1a. Objectives (from AD-416)
1. Determine how specific foods, specific components of foods of particular patterns or dietary intake are related to eye health. 2. Identify nutritional etiologic factors that are causally related to onset, prevalence and progress of age-related macular degeneration and cataract. Design diets, dietary supplements or natural reagents to delay these diseases. 3. Identify mechanisms by which retina and lens function are maintained throughout life.
1b. Approach (from AD-416)
The objectives of the Laboratory for Nutrition and Vision Research are to find nutritional means to diminish the prevalence or delay the onset or progress of age-related eye diseases such as cataract and age-related macular degeneration. These are the major blinding diseases. We approach these objectives using epidemiologic and laboratory techniques. At present we are analyzing nutritional, ophthalmologic and genetic data from about 15,000 people. Studies in the laboratory are oriented to determine the pathobiologic mechanisms that underlie the epidemiologic observations. Thus, we are trying to understand how consuming a diet that provides high levels of readily digested carbohydrate (dietary glycemic index) is related to increased risk for macular degeneration and cataract. We are also trying to understand why antioxidants confer visual benefit. A complementary aspect of this work involves elucidation how the proteolytic machinery specifically, and the protein quality control machinery in general, is related to maintaining proper protein quality within lens and retina cells. Another aspect of this work involves trying to understand how this proteolytic machinery controls tissue formation and integrity and how its function is related to nutrition.
3. Progress Report
This progress report includes the work of a subordinate project at the HNRCA funded through a Specific Cooperative Agreement with TUFTS UNIVERSITY. For further information and progress report, see 1950-51000-075-02S (Using Nutrition and Proteolysis to Delay Age-Related Macular Degeneration and Cataracts.)
1. New associations between risk for age-related macular degeneration and diet. Americans now eat more than 200 additional calories per day than we did in 1970. Most of these come from readily digested carbohydrates. Age-related macular degeneration (AMD) afflicts >1.5 million Americans and the rates are growing exponentially. Exacerbating this situation, there are no widespread treatments for AMD. ARS-funded researchers at JMUSDA-HNRCA at Tufts University, Boston, MA, found that consuming lower GI diets offers protection against the onset and progress of AMD. The glycemic index measures how fast sugar is absorbed into the blood after eating a food that contains carbohydrate. We predict that we can save the sight of over 100,000 Americans by lowering slightly the glycemic index of the diet. Importantly, the benefits accrued from consuming lower GI diets are in addition to the advantages gained from consuming higher levels of antioxidants or omega 3 fatty acids. These data are useful guides for the production and marketing of healthier foods.
2. New animal model shows that diets with lower amounts of simple sugars delay age-related macular degeneration (AMD). Age-related macular degeneration (AMD) afflicts more than 1.5 million Americans. The rates are growing exponentially and there are no widespread treatments for AMD. It is estimated that if we could delay onset or progress of AMD by only 10 years a significant proportion of AMD would not become of medical significance. ARS-funded researchers at JMUSDA-HNRCA at Tufts University, Boston, MA, found that by feeding mice diets comparable to the high glycemic index (GI) diets, (higher in simple sugars) that Americans consume, we observed the onset of many of the features of early AMD. Importantly, we were able to delay the onset and progress of these features by feeding the animals lower GI diets. Interestingly, mice that consume the same amount of calories, but in a lower GI diet, are thinner, bringing additional health advantages that are of keen interest to Americans. These data confirm that consuming lower GI diets, which are lower in simple sugars, affords advantage with respect to eye health.
3. Discovering how to prolong lens and retina function. Damaged proteins accumulate in tissues due to stresses of exposure to oxygen and other biproducts of usual metabolism. These damaged proteins are cytotoxic- compromising the function of the cells and tissues in which they accumulate. The retina and lens have a very active protein degrading machinery. But these activities are diminished upon aging. ARS-funded researchers at JMUSDA-HNRCA at Tufts University, Boston, MA, observed how stress due to exposure of the lens and retina cells to sugar diminishes the ability of the proteolytic machinery to function, thus compromising the cells. They also note how these systems can be prolonged and activated, offering an ability to extend function of the cells and tissues. They also showed how some of the protein degrading machinery is used to establish lens clarity, solving, in part, an enigma that puzzled developmental biologists for over 100 years. These discoveries will lead to novel therapies of AMD and cataracts.
Dudek, E.J., Lampi, K.J., Lampi, J., Shang, F., King, J., Wang, Y., Taylor, A. 2010. Ubiquitin proteasome pathway-mediated degradation of proteins: effects due to site-specific substrate deamidation. Investigative Ophthalmology and Visual Science. 51(8):4164-4173.